title: The unique expression and function of miR-424 in human placental trophoblasts.
abstract: Placental hypoperfusion causes cellular hypoxia and is associated with fetal growth restriction and preeclampsia. In response to hypoxia, the repertoire of genes expressed in placental trophoblasts changes, which influences key cellular processes such as differentiation and fusion. Diverse miRNAs were recently found to modulate the cellular response to hypoxia. Here we show that miR-424, which was previously shown to be upregulated by hypoxia in nontrophoblastic cell types, is uniquely downregulated in primary human trophoblasts by hypoxia or chemicals known to hinder cell differentiation. We also identify FGFR1 as a direct target of miR-424 in human trophoblasts. This effect is unique to miR-424 and is not seen with other members of this miRNA family that are expressed in trophoblasts, such as miR-15 and miR-16. Our findings establish a unique role for miR-424 during differentiation of human trophoblasts.
authors.affiliation: Magee-Womens Research Institute, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh, Pennsylvania 15213, USA.
authors.forename: Jean-Francois
authors.initials: JF
authors.lastname: Mouillet
authors.forename: Rogier B
authors.initials: RB
authors.lastname: Donker
authors.forename: Takuya
authors.initials: T
authors.lastname: Mishima
authors.forename: Tina
authors.initials: T
authors.lastname: Cronqvist
authors.forename: Tianjiao
authors.initials: T
authors.lastname: Chu
authors.forename: Yoel
authors.initials: Y
authors.lastname: Sadovsky
mesh_terms: D002454:Cell Differentiation / Q000235:genetics; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D015536:Down-Regulation; D005260:Female; D006801:Humans; D000860:Hypoxia / Q000378:metabolism*; D048369:MAP Kinase Kinase 1 / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D010920:Placenta / Q000166:cytology / Q000378:metabolism*; D011247:Pregnancy; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics / Q000378:metabolism; D014327:Trophoblasts / Q000166:cytology / Q000378:metabolism*
chemical_list: C554214:MIRN424 microrna, human; D035683:MicroRNAs; C496348:FGFR1 protein, human; D051496:Receptor, Fibroblast Growth Factor, Type 1; D048369:MAP Kinase Kinase 1
keywords: FGFR1; hypoxia; miR-424; microRNA; trophoblasts